Low-Intensity Pulsed Ultrasound Alleviates Hypoxia-Induced Chondrocyte Damage in Temporomandibular Disorders by Modulating the Hypoxia-Inducible Factor Pathway
Temporomandibular disorders are a common cause of chronic pain in the orofacial region and have a complex and multi-factorial pathophysiology. Mechanical loading or inflammatory conditions have been shown to decrease oxygen tension within the joint cartilage and activate the hypoxia-inducible factor...
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.00689/full |
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| author | Tao Yang Chao Liang Lei Chen Lei Chen Jun Li Jun Li Wei Geng |
| author_facet | Tao Yang Chao Liang Lei Chen Lei Chen Jun Li Jun Li Wei Geng |
| author_sort | Tao Yang |
| collection | DOAJ |
| description | Temporomandibular disorders are a common cause of chronic pain in the orofacial region and have a complex and multi-factorial pathophysiology. Mechanical loading or inflammatory conditions have been shown to decrease oxygen tension within the joint cartilage and activate the hypoxia-inducible factor (HIF) pathway, which in turn aggravates the pathological processes underlying temporomandibular joint (TMJ) disorders. We previously showed that low-intensity pulsed ultrasound (LIPUS) treatment effectively repairs TMJ injury induced by chronic sleep deprivation (CSD). Here, we explored the effects of LIPUS treatment on hypoxia-induced chondrocyte injury. We found that it effectively restored the proliferation capacity of mandibular chondrocytes under hypoxic conditions and lowered their rate of apoptosis. Chondrogenic capacity, as assessed by type II collagen levels, and mucin-positive areas were also significantly increased after LIPUS treatment. Levels of matrix metalloprotein-3 and interleukin-6 decreased in mandibular chondrocytes following this treatment, whereas the expression of tissue inhibitor of metalloproteinase-1 increased. We also found that HIF-1α expression was upregulated in mandibular chondrocytes under hypoxic conditions and was further enhanced by LIPUS treatment. Similarly, HIF-2α levels increased in mandibular chondrocytes under hypoxic conditions but decreased following LIPUS treatment. Subsequently, we established a CSD-induced TMJ injury model and found that LIPUS increased mucin-positive areas as well as HIF-1α expression and decreased HIF-2 level in the chondrocyte layer. Together, our results indicate that the protective effect of LIPUS on chondrocyte is partly associated with the HIF pathway. |
| first_indexed | 2024-12-19T15:40:44Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-19T15:40:44Z |
| publishDate | 2020-05-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-cd8324031dbc4811a62e332f3aae90ba2022-12-21T20:15:28ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-05-011110.3389/fphar.2020.00689528672Low-Intensity Pulsed Ultrasound Alleviates Hypoxia-Induced Chondrocyte Damage in Temporomandibular Disorders by Modulating the Hypoxia-Inducible Factor PathwayTao Yang0Chao Liang1Lei Chen2Lei Chen3Jun Li4Jun Li5Wei Geng6Department of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, ChinaDepartment of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, ChinaDepartment of Orthodontics, School of Stomatology, Shandong University, Jinan, ChinaShandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, ChinaDepartment of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, ChinaDepartment of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, ChinaTemporomandibular disorders are a common cause of chronic pain in the orofacial region and have a complex and multi-factorial pathophysiology. Mechanical loading or inflammatory conditions have been shown to decrease oxygen tension within the joint cartilage and activate the hypoxia-inducible factor (HIF) pathway, which in turn aggravates the pathological processes underlying temporomandibular joint (TMJ) disorders. We previously showed that low-intensity pulsed ultrasound (LIPUS) treatment effectively repairs TMJ injury induced by chronic sleep deprivation (CSD). Here, we explored the effects of LIPUS treatment on hypoxia-induced chondrocyte injury. We found that it effectively restored the proliferation capacity of mandibular chondrocytes under hypoxic conditions and lowered their rate of apoptosis. Chondrogenic capacity, as assessed by type II collagen levels, and mucin-positive areas were also significantly increased after LIPUS treatment. Levels of matrix metalloprotein-3 and interleukin-6 decreased in mandibular chondrocytes following this treatment, whereas the expression of tissue inhibitor of metalloproteinase-1 increased. We also found that HIF-1α expression was upregulated in mandibular chondrocytes under hypoxic conditions and was further enhanced by LIPUS treatment. Similarly, HIF-2α levels increased in mandibular chondrocytes under hypoxic conditions but decreased following LIPUS treatment. Subsequently, we established a CSD-induced TMJ injury model and found that LIPUS increased mucin-positive areas as well as HIF-1α expression and decreased HIF-2 level in the chondrocyte layer. Together, our results indicate that the protective effect of LIPUS on chondrocyte is partly associated with the HIF pathway.https://www.frontiersin.org/article/10.3389/fphar.2020.00689/fullchondrocytehypoxialow-intensity pulsed ultrasound (LIPUS)hypoxia-inducible factors (HIFs)temporomandibular joint disorder (TMD) |
| spellingShingle | Tao Yang Chao Liang Lei Chen Lei Chen Jun Li Jun Li Wei Geng Low-Intensity Pulsed Ultrasound Alleviates Hypoxia-Induced Chondrocyte Damage in Temporomandibular Disorders by Modulating the Hypoxia-Inducible Factor Pathway Frontiers in Pharmacology chondrocyte hypoxia low-intensity pulsed ultrasound (LIPUS) hypoxia-inducible factors (HIFs) temporomandibular joint disorder (TMD) |
| title | Low-Intensity Pulsed Ultrasound Alleviates Hypoxia-Induced Chondrocyte Damage in Temporomandibular Disorders by Modulating the Hypoxia-Inducible Factor Pathway |
| title_full | Low-Intensity Pulsed Ultrasound Alleviates Hypoxia-Induced Chondrocyte Damage in Temporomandibular Disorders by Modulating the Hypoxia-Inducible Factor Pathway |
| title_fullStr | Low-Intensity Pulsed Ultrasound Alleviates Hypoxia-Induced Chondrocyte Damage in Temporomandibular Disorders by Modulating the Hypoxia-Inducible Factor Pathway |
| title_full_unstemmed | Low-Intensity Pulsed Ultrasound Alleviates Hypoxia-Induced Chondrocyte Damage in Temporomandibular Disorders by Modulating the Hypoxia-Inducible Factor Pathway |
| title_short | Low-Intensity Pulsed Ultrasound Alleviates Hypoxia-Induced Chondrocyte Damage in Temporomandibular Disorders by Modulating the Hypoxia-Inducible Factor Pathway |
| title_sort | low intensity pulsed ultrasound alleviates hypoxia induced chondrocyte damage in temporomandibular disorders by modulating the hypoxia inducible factor pathway |
| topic | chondrocyte hypoxia low-intensity pulsed ultrasound (LIPUS) hypoxia-inducible factors (HIFs) temporomandibular joint disorder (TMD) |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.00689/full |
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